Quinoline-sulfonamides as a multi-targeting neurotherapeutic for cognitive decline: in vitro, in silico studies and ADME evaluation of monoamine oxidases and cholinesterases inhibitors.

ABSTRACT: Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved. In the treatment of AD, multifunctional agents targeting cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have shown promising results. Herein, a series of novel quinoline-sulfonamides (a1-18) were designed and synthesized as a dual inhibitor of MAOs and ChEs. The in vitro results showed that compounds a5, a12, a11, and a6 exhibited the most potent compounds against specific enzymes. They had IC₅₀ value 0.59 ± 0.04 for MAO-A, 0.47 ± 0.03 for MAO-B, 0.58 ± 0.05 for BChE and 1.10 ± 0.77 for AChE μM respectively. Furthermore, kinetic studies revealed that these compounds are competitive. Molecular docking studies enhanced the understanding of the in s

SUBMITTER: Jalil S 

PROVIDER: S-EPMC10941260 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature